Tumour necrosis factor-alpha infusion produced insulin resistance but no change in the incretin effect in healthy volunteers

Signe Tellerup Nielsen, Louise Lehrskov-Schmidt, Rikke Krogh-Madsen, Thomas P J Solomon, Lars Lehrskov-Schmidt, Jens Juul Holst, Kirsten Møller

Research output: Contribution to journalArticlepeer-review

19 Citations (Scopus)


BACKGROUND: Type 2 diabetes mellitus (T2DM) is associated with peripheral insulin resistance, impaired incretin effect, and increased plasma levels of tumour necrosis factor-alpha (TNF-α). Although TNF-α infusion at a dose that induces systemic inflammation in healthy volunteers has been demonstrated to induce peripheral insulin resistance, the influence of this cytokine on the incretin effect is unknown.

METHODS: We investigated whether systemic inflammation induced by TNF-α infusion in healthy volunteers alters the incretin hormone response to oral and intravenous glucose loads in a crossover study design with ten healthy male volunteers (mean age 24 years, mean body mass index 23.7 kg/m(2) ). The study consisted of four study days: days 1 and 2, 6-h infusion of saline; days 3 and 4, 6-h infusion of TNF-α; days 1 and 3, 4-h oral glucose tolerance test; and days 2 and 4, 4-h corresponding intravenous isoglycaemic glucose tolerance test. Glucose tolerance tests were initiated after 2 h of saline/TNF-α infusion. Plasma concentrations of TNF-α, interleukin 6, glucose, incretin hormones, and cortisol, and serum concentrations of C-peptide and insulin were measured throughout the study days. Insulin sensitivity was estimated by the Matsuda index and homeostasis model assessment of insulin resistance (HOMA-IR). Prehepatic insulin secretion rates were calculated.

RESULTS: TNF-α infusion induced symptoms of systemic inflammation; increased plasma levels of cortisol, TNF-α, and interleukin 6; and increased the HOMA-IR. The secretion of incretin hormones as well as the incretin effect remained unchanged.

CONCLUSION: In healthy young male volunteers, acute systemic inflammation induced by infusion of TNF-α is associated with insulin resistance with no change in the incretin effect.

Original languageEnglish
Pages (from-to)655-63
Number of pages9
JournalDiabetes/metabolism research and reviews
Issue number8
Publication statusPublished - Nov 2013

Bibliographical note

Copyright © 2013 John Wiley & Sons, Ltd.


  • Adolescent
  • Adult
  • Blood Glucose
  • C-Peptide
  • Cross-Over Studies
  • Cytokines
  • Glucose Tolerance Test
  • Healthy Volunteers
  • Humans
  • Hydrocortisone
  • Incretins
  • Inflammation
  • Insulin
  • Insulin Resistance
  • Male
  • Tumor Necrosis Factor-alpha
  • Young Adult


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